Original Research ARTICLE
A proof of concept clinical trial for the single luteal use of long-acting GnRH-antagonist degarelix in controlled ovarian stimulation for in vitro fertilization; Long Antagonist protocol
- 13rd OB GYN Department, Aristotle University of Thessaloniki, Greece
- 2Hacettepe University, Turkey
- 3IVF department, Assisting Nature IVF Clinic, Greece
- 4Hôpital Jean-Verdier, France
- 5University Hospital Brussels, Belgium
Introduction: A drawback with GnRH antagonist protocols in IVF is they have limited flexibility in cycle programming. This proof of concept study explored the efficacy of a single dose, long-acting GnRH antagonist IVF protocol. Trial registration number: NCT03240159, retrospectively registered, 08-03-2017.
Materials & Methods: The efficacy of a single dose long-acting antagonist, Degarelix, was explored initially in healthy donors first and subsequently in infertile patients. In the first part, 5 healthy oocyte donors underwent ovarian stimulation with this new protocol: in the late luteal phase, at Day 24, a bolus injection of degarelix was administered subcutaneously to control the LH surge in the follicular phase. Ovarian stimulation with gonadotropins was initiated subsequently from day 7 to day-10. Endpoints were firstly to inhibit the LH surge later in the follicular phase and, secondly, to retrieve mature oocytes for in vitro fertilization. In the second part, 5 infertile women received the same bolus injection of degarelix administered during the luteal phase at Day 24. Different gonadotropin starting days (day-2 through day-8) were tested in order to observe possible differences in ovarian stimulation. In these infertile patients fresh embryo transfers were performed to assess the pregnancy efficacy of this protocol on pregnancy outcomes and to address any possible negative effects on endometrium receptivity.
Results: In the first part of the study, all donors were effectively downregulated with a single luteal dose of degarelix 0.5 mL for up to 22 days until the final oocyte maturation triggering day. Mature oocytes were retrieved 36 hours later from all patients and all produced 2-7 blastocysts. In the second part, all five infertile patients achieved sufficient LH downregulation and completed ovarian stimulation without any LH surge. All patients (except one with freeze all strategy) had blastocysts transferred and pregnancy occurred in 3 out of 5 women
Conclusion: A single dose of the long-acting antagonist degarelix during the luteal phase appears to be effective in down-regulating hypophysis during ovarian stimulation. This represents a possible new protocol for IVF, which should be further elucidated in RCTs
Keywords: IVF, Antagonist protocol, Degarelix, ovarian stimulation, long agonist protocol, Pregnancy
Received: 05 Nov 2017;
Accepted: 19 Jan 2018.
Edited by:Carlo Alviggi, University of Naples Federico II, Italy
Reviewed by:Sandro C. Esteves, Androfert, Andrology and Human Reproduction Clinic, Brazil
Alessandro Conforti, University of Naples Federico II, Italy
Copyright: © 2018 PAPANIKOLAOU, Yarali, Timotheou, Grynberg, Zafeiratis, Tournaye and Najdecki. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: MD, PhD. EVANGELOS G. PAPANIKOLAOU, Aristotle University of Thessaloniki, 3rd OB GYN Department, Thessaloniki, Greece, email@example.com